Needle-free jet injection provides an equally effective alternate route for the administration of drugs that is free of many of the problems associated with conventional delivery using a needle and syringe (e.g., needle stick injections, expense associated with disposal of sharps, belonephobia, and compliance). Jet injectors can be classified by the actuator used to generate the high pressures required for injection; ranging from 5.5 MPa to ˜30 MPa dependent on the size of the orifice, the desired depth of injection, the viscosity of the drug, and individual skin variation.
A continuing issue with drug delivery using needle-free jet injectors is repeatable delivery of a specific amount of active drug to the target tissue. Commercial devices powered by springs or compressed gases have little to no control over the pressure applied to the drug during the time course of the injection, potentially resulting in shearing and loss of activity of larger therapeutic protein molecules. Furthermore, these devices are often loud and sometimes deemed painful. While some pressure pulse shaping may be afforded by using variable gas orifices and fast/slow pyrotechnic charges, these techniques, while an improvement, may not provide precise control. More recently, Stachowiak et al. developed a jet injector that uses a dynamically controllable piezoelectric stack placed within a mechanical flexure. By decoupling the depth and dose functions of the jet injector, they have demonstrated that penetration depth in tissue model materials (i.e. acrylamide) may be precisely controlled by adjusting the proportion of the injection volume delivered at high speed. However, the piston stroke and hence the volume of fluid delivered may be limited by the design, which is difficult to scale.
An electrically driven linear Lorentz-force motor, affords robust and precise control over coil position and thereby over both the depth and volume of drug delivered without compromising stroke (e.g., 25 mm in current device) and therefore volume (e.g., 250 μL in current device). See B. Hemond, D. M. Wendell, N. C. Hogan, A. J. Taberner, and I. W. Hunter, “A Lorentz-force actuated autoloading needle-free injector,” in: Proceedings of the 28th Annual International Conference of the Engineering Medicine and Biology Society 1 (2006) 679-682, http://ieeexplore.ieee.org/hemond, and A. J Taberner, N. B. Ball, N. C. Hogan, and I. W. Hunter, “A portable needle-free jet injector based on a custom high power-density voice-coil actuator,” in: Proceedings of the 28th Annual International Conference of the Engineering Medicine and Biology Society 1 (2006) 5001-4, http://ieeexplore.ieee.org/taberner; both references are incorporated herein in their entireties.
Energy delivered to the actuator in an electrical form allows one to impose a time varying pressure (or velocity) profile (i.e., waveform) on the drug volume during the course of the injection through the use of a monitored and servo controlled amplifier. See Hemond et al. and Taberner et al., and also B. Hemond, A. Taberner, C. Hogan, B. Crane, and I. Hunter, “Development and performance of a controllable autoloading needle-free jet injector,” J Med Devices 5 (2010) 015001-1-015001-7, both references are incorporated by reference herein in their entireties.
Controlling the volume of drug delivered ensures that the relevant dose is delivered (e.g., insulin), potentially reduces the dose (e.g., ID delivery of vaccines normally administered intramuscularly [IM] or subcutaneously [SC]) and cost for each deliverable, and increases the availability of drugs in limited supply (e.g., vaccines). Controlling the depth of injection ensures delivery to the appropriate tissue layer regardless of body type and enables more accurate delivery of certain drugs that are most effective when delivered SC (e.g., insulin) or IM (e.g., tetanus) or when delivered ID at normal or reduced volume (e.g., lidocaine, TB, rabies, HBV, influenza, etc.).
Typically, jet injectors are used to propel liquid (e.g., insulin, human growth hormone, etc.), reconstituted drug formulations (e.g., vaccines, MAbs), powdered drug, or drug coated particles (e.g., inert gold particles) into the target tissue. However, concomitant with the continual development of protein-based therapeutics and vaccines has been the development of new drug formulations to enhance delivery, stability, and efficacy (i.e., bioavailability) and a need for more innovative methods of delivery.
Environmentally responsive systems (e.g., hydrogels), liposomes, and biodegradable polymers, both bulk (e.g., polylactides, polyglycolides, and their copolymers) and surface erodible materials, have attempted to address this need by providing controlled release systems thereby greatly reducing the frequency of dosing. However, delivery often involves invasive implantation.
While several studies have reported using the PowderJect device, currently owned by PowderJect Vaccines, Inc., to assess epidermal powder immunization using gold coated particles (1.5 to 2.5 μm is size), vaccine formulations, etc., little work has been done on evaluating the use of jet injectors to deliver biodegradable polymeric/drug controlled release formulations. A spring-actuated device has been proposed for delivering a preferred biodegradable pioneer projectile and subsequent therapeutic, together referred to as an injectate to a human or animal. However, unlike the linear Lorentz-force actuated jet injector described herein, springs provide little to no control over the pressure vs. time profile, a requisite for delivery to specific target tissues/body locations in a heterogeneous population.
There is a need for improved targeting of drug to specific sites combined with the controlled release of drug from these delivered bodies, to thereby increase drug efficacy and reduce repeated dosing.